The goal of this proposal is to clarify, primarily by fine structural techniques, important gaps in our understanding of the functional organization of synapses and neuronal cytoplasm and of the behavior and interactions of contractile proteins of muscle cells. The first objective is to define further the organization and distribution of receptor molecules in postsynaptic membranes by use of an in situ negative staining technique that has proved superior to conventional preparative methods. This approach will be used to investigate directly the change in acetylcholine receptor distribution following surgical denervation in mammalian muscle, and the organizaton of acetylcholine-and other rceptors in cholinergic and non-cholinergic arthropod muscles. Secondly, a systematic attempt will be made to achieve fine structural localization of actin filaments in neurons by heavy-meromyosin labelling, with minimal disruption of cytoplasmic architecture and notably of microtubules and membrane-limited structures. Selection of the insect central nerve cord for this work is prompted by its cellular disposition and small size, potentially facilitating access of the marker to the cytoplasm and procedures other than extended glycerination will be assayed for their ability to improve preservation of cytoplamsic structures while permitting actin labelling. The aim of this work is to consider further the possible role of this contractile protein in axoplasmic transport. This third objective is to extend our previous studies on interactions between muscle actin and myosin which resulted in the in vitro formation of a 'contractile unit', in a number of respects comparable with that of intact muscle. Experiments are designed to elucidate further the factors controlling the morphogenesis of the sarcomere.